Role of matrix metalloproteinases in the development of airway inflammation and remodeling

Matrix metalloproteinases (MMPs) are a major group of proteases known to regulate extracellular matrix (ECM) turnover and so they have been suggested to be important in the process of lung disease associated with tissue remodeling. This has led to the concept that modulation of airway remodeling including excessive proteolysis damage to the tissue may be of interest for future treatment. Within the MMP family, macrophage elastase (MMP-12) is able to degrade ECM components such as elastin and is involved in tissue remodeling processes in chronic obstructive pulmonary disease including emphysema. Pulmonary fibrosis has an aggressive course and is usually fatal within an average of 3 to 6 years after the onset of symptoms. Pulmonary fibrosis is associated with deposition of ECM components in the lung interstitium. The excessive airway remodeling as a result of an imbalance in the equilibrium of the normal processes of synthesis and degradation of ECM components could justify anti-protease treatments. Indeed, the correlation of the differences in hydroxyproline levels in the lungs of bleomycin-treated mice strongly suggests that a reduced molar pro-MMP-9/TIMP-1 ratio in bronchoalveolar lavage fluid is associated with collagen deposition, beginning as early as the inflammatory events at day 1 after bleomycin administration. Finally, these observations emphasize that effective treatment of these disorders must be started early during the natural history of the disease, prior to the development of extensive lung destruction and fibrosis.

A conceptual and practical overview of cDNA microarray technology: implications for basic and clinical sciences

cDNA microarray is an innovative technology that facilitates the analysis of the expression of thousands of genes simultaneously. The utilization of this methodology, which is rapidly evolving, requires a combination of expertise from the biological, mathematical and statistical sciences. In this review, we attempt to provide an overview of the principles of cDNA microarray technology, the practical concerns of the analytical processing of the data obtained, the correlation of this methodology with other data analysis methods such as immunohistochemistry in tissue microarrays, and the cDNA microarray application in distinct areas of the basic and clinical sciences.

Striatal and extrastriatal atrophy in Huntington's disease and its relationship with length of the CAG repeat

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder that affects the striatum most severely. However, except for juvenile forms, relative preservation of the cerebellum has been reported. The objective of the present study was to perform MRI measurements of caudate, putamen, cerebral, and cerebellar volumes and correlate these findings with the length of the CAG repeat and clinical parameters. We evaluated 50 consecutive patients with HD using MRI volumetric measurements and compared them to normal controls. Age at onset of the disease ranged from 4 to 73 years (mean: 43.1 years). The length of the CAG repeat ranged from 40 to 69 (mean: 47.2 CAG). HD patients presented marked atrophy of the caudate and putamen, as well as reduced cerebellar and cerebral volumes. There was a significant correlation between age at onset of HD and length of the CAG repeat, as well as clinical disability and age at onset. The degree of basal ganglia atrophy correlated with the length of the CAG repeat. There was no correlation between cerebellar or cerebral volume and length of the CAG repeat. However, there was a tendency to a positive correlation between duration of disease and cerebellar atrophy. While there was a negative correlation of length of the CAG repeat with age at disease onset and with striatal degeneration, its influence on extrastriatal atrophy, including the cerebellum, was not clear. Extrastriatal atrophy occurs later in HD and may be related to disease duration.

Prevalence of vascular-endothelial growth factor, matrix metalloproteinases and tissue inhibitors of metalloproteinases in primary breast cancer

Our objective was to determine the presence of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and MMP-9 and specific tissue inhibitors of matrix metalloproteinase (TIMP-1 and TIMP-2) in tumor samples obtained from patients with primary breast cancer. We attempted to correlate these findings with the status of the sentinel lymph node (SLN) and clinical-pathological characteristics such as age, tumor size, histological type, histological grade, and vascular invasion. Tumor samples from 88 patients with primary breast cancer were analyzed. The immunoreactivity of VEGF, MMP-2, MMP-9, TIMP-1, and TIMP-2 in tumors was correlated with clinical and pathological features, as well as SLN status. Nonparametric, Mann-Whittney, Kruskal-Wallis, and Spearmann tests were used. Categorical variables were analyzed by the Pearson test. No statistically significant correlation was found between the amount of VEGF, MMP-2, MMP-9, TIMP-1, and TIMP-2 and the presence of tumor cells in the SLN. However, larger tumor diameter (P < 0.01) and the presence of vascular invasion (P < 0.01) were correlated positively with a positive SLN. A significant correlation of higher VEGF levels (P = 0.04) and lower TIMP-1 levels (P = 0.04) with ductal histology was also observed. Furthermore, lower TIMP-2 levels showed a statistically significant correlation with younger age (<50 years) and larger tumor diameter (2.0-5.0 cm). A positive SLN correlated significantly with a larger tumor diameter and the presence of vascular invasion. Higher VEGF and lower TIMP-1 levels were observed in patients with ductal tumors, while higher TIMP-1 levels were observed in lobular tumors.

Reversible flow of cholesteryl ester between high-density lipoproteins and triacylglycerol-rich particles is modulated by the fatty acid composition and concentration of triacylglycerols

We determined the influence of fasting (FAST) and feeding (FED) on cholesteryl ester (CE) flow between high-density lipoproteins (HDL) and plasma apoB-lipoprotein and triacylglycerol (TG)-rich emulsions (EM) prepared with TG-fatty acids (FAs). TG-FAs of varying chain lengths and degrees of unsaturation were tested in the presence of a plasma fraction at d > 1.21 g/mL as the source of CE transfer protein. The transfer of CE from HDL to FED was greater than to FAST TG-rich acceptor lipoproteins, 18% and 14%, respectively. However, percent CE transfer from HDL to apoB-containing lipoproteins was similar for FED and FAST HDL. The CE transfer from HDL to EM depended on the EM TG-FA chain length. Furthermore, the chain length of the monounsaturated TG-containing EM showed a significant positive correlation of the CE transfer from HDL to EM (r = 0.81, P < 0.0001) and a negative correlation from EM to HDL (r = -041, P = 0.0088). Regarding the degree of EM TG-FAs unsaturation, among EMs containing C18, the CE transfer was lower from HDL to C18:2 compared to C18:1 and C18:3, 17.7%, 20.7%, and 20%, respectively. However, the CE transfer from EMs to HDL was higher to C18:2 than to C18:1 and C18:3, 83.7%, 51.2%, and 46.3%, respectively. Thus, the EM FA composition was found to be the rate-limiting factor regulating the transfer of CE from HDL. Consequently, the net transfer of CE between HDL and TG-rich particles depends on the specific arrangement of the TG acyl chains in the lipoprotein particle core.

Detection of acute cerebral hemorrhage in rabbits by magnetic induction

Acute cerebral hemorrhage (ACH) is an important clinical problem that is often monitored and studied with expensive devices such as computed tomography, magnetic resonance imaging, and positron emission tomography. These devices are not readily available in economically underdeveloped regions of the world, emergency departments, and emergency zones. We have developed a less expensive tool for non-contact monitoring of ACH. The system measures the magnetic induction phase shift (MIPS) between the electromagnetic signals on two coils. ACH was induced in 6 experimental rabbits and edema was induced in 4 control rabbits by stereotactic methods, and their intracranial pressure and heart rate were monitored for 1 h. Signals were continuously monitored for up to 1 h at an exciting frequency of 10.7 MHz. Autologous blood was administered to the experimental group, and saline to the control group (1 to 3 mL) by injection of 1-mL every 5 min. The results showed a significant increase in MIPS as a function of the injection volume, but the heart rate was stable. In the experimental (ACH) group, there was a statistically significant positive correlation of the intracranial pressure and MIPS. The change of MIPS was greater in the ACH group than in the control group. This high-sensitivity system could detect a 1-mL change in blood volume. The MIPS was significantly related to the intracranial pressure. This observation suggests that the method could be valuable for detecting early warning signs in emergency medicine and critical care units.

Downregulation of TIM-3 mRNA expression in peripheral blood mononuclear cells from patients with systemic lupus erythematosus

The T-cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its expression level in the immune cells of systemic lupus erythematosus (SLE) patients is not known. The aim of this study was to investigate whether the expression of TIM-3 mRNA is associated with pathogenesis of SLE. Quantitative real-time reverse transcription-polymerase chain reaction analysis (qRT-PCR) was used to determine TIM-1, TIM-3, and TIM-4 mRNA expression in peripheral blood mononuclear cells (PBMCs) from 132 patients with SLE and 62 healthy controls. The PBMC surface protein expression of TIMs in PBMCs from 20 SLE patients and 15 healthy controls was assayed by flow cytometry. Only TIM-3 mRNA expression decreased significantly in SLE patients compared with healthy controls (P<0.001). No significant differences in TIM family protein expression were observed in leukocytes from SLE patients and healthy controls (P>0.05). SLE patients with lupus nephritis (LN) had a significantly lower expression of TIM-3 mRNA than those without LN (P=0.001). There was no significant difference in the expression of TIM-3 mRNA within different classes of LN (P>0.05). Correlation of TIM-3 mRNA expression with serum IgA was highly significant (r=0.425, P=0.004), but was weakly correlated with total serum protein (rs=0.283, P=0.049) and serum albumin (rs=0.297, P=0.047). TIM-3 mRNA expression was weakly correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; rs=-0.272, P=0.032). Our results suggest that below-normal expression of TIM-3 mRNA in PBMC may be involved in the pathogenesis of SLE.

Microstructural changes of frozen strawberries submitted to pre-treatments with additives and vacuum impregnation

Strawberries were submitted to freezing after pre-treatments with hydrocolloid and calcium salts (pectin and calcium chloride) at different concentrations, in the attempt to establish a correlation of the effects of these substances and their processing, on the physical and microstructural characteristics of fruits after thawing. Strawberry halves were submitted to impregnation with controlled vacuum pressure of 84.4, 50.5 and 16.6 kPa; comprising pectin at concentrations of 0, 1.5 and 3%; with the addition of calcium chloride at concentrations of 0, 3 and 6%; and glucose at 20%, for 4 hours. Measurements were made of the total soluble solid contents, cellular fluid loss, texture and viscosity of the solution, before and after the freezing/thawing. Images of the tissue cuts during the freezing, in function of time, were taken in an optic microscope coupled to a cold-stage and controlled temperature system, where the reduction of the cellular area was quantified using an image analyzing software. The pectin concentration had an influence on and demonstrated a potential for protection of the frozen tissue samples. The photomicrographs showed that the loss of cellular fluid occurs during the growth of ice formed in the intercellular spaces and it is retarded through treatments with high pectin concentrations.

Quality indicators and shelf life of red octopus (Octopus maya) in chilling storage

Abstract There are no precedents concerning the quality of Octopus maya during chilled storage. This study evaluated the shelf life of the red octopus in chilling storage (4oC) and the correlation of the sensory quality index with microbiological counting and the biochemical indicators (hypoxanthine, histamine and volatile amines). A total of 112 whole raw octopi (average weight of 896 g) were randomly selected from seven batches and exposed to 4°C for 18, 24, 48, 72, 84, 96, and 100 h. The histamine concentration (91.7%), followed by the counts of psychrotrophic bacteria (5.5%) and hypoxanthine (2.2%), were the predictors from the redundancy analysis that better explained the changes taking place during the chilling hours. After 72 h of chilling, the microbial count was determined to be log 4.7 CFU/g, and the octopus samples were classified as B quality (minor sensory quality defects) based on the sensory quality scale. Although the samples were not classified as unacceptable at 100 h of refrigeration by the sensory index, the level of histamine reached the defect action level (5 mg/100 g) as ruled by the International Food Safety Authorities. The shelf life of the red octopus in chilling storage was predicted to be 119 h.

Spatial variability of soil fertility and its relationship with seed physiological potential in a soybean production area

The correlation of soil fertility x seed physiological potential is very important in the area of seed technology but results published with that theme are contradictory. For this reason, this study to evaluate the correlations between soil chemical properties and physiological potential of soybean seeds. On georeferenced points, both soil and seeds were sampled for analysis of soil fertility and seed physiological potential. Data were assessed by the following analyses: descriptive statistics; Pearson's linear correlation; and geostatistics. The adjusted parameters of the semivariograms were used to produce maps of spatial distribution for each variable. Organic matter content, Mn and Cu showed significant effects on seed germination. Most variables studied presented moderate to high spatial dependence. Germination and accelerated aging of seeds, and P, Ca, Mg, Mn, Cu and Zn showed a better fit to spherical semivariogram: organic matter, pH and K had a better fit to Gaussian model; and V% and Fe showed a better fit to the linear model. The values for range of spatial dependence varied from 89.9 m for P until 651.4 m for Fe. These values should be considered when new samples are collected for assessing soil fertility in this production area.